Prevention of death in mice infected with coxsackievirus A16 using guanidine HCl mixed with substituted benzimidazoles |
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Authors: | E C Herrmann J A Herrmann D C Delong |
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Affiliation: | 1. Department of Basic Sciences, University of Illinois, Peoria School of Medicine, P.O. Box 1649, Peoria, IL 61656, U.S.A.;2. Mobilab Inc., Peoria, IL 61615, U.S.A.;3. Lilly Research Laboratories, Indianapolis, IN 46206, U.S.A. |
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Abstract: | A significant reduction in the death rate of infant mice infected with ten 50% lethal doses (LD50) of coxsackievirus A16 was observed when they were treated 58 h after infection with two injections of guanidine at 145 mg/kg per injection. Tremors occurred at this level but disappeared after treatment was discontinued. Tremors were apparent, but less severe at 97 mg/kg per injection and did not occur at 48 mg/kg per injection. No antiviral effect could be detected at either of these levels of guanidine. When an inactive level of guanidine (97 mg/kg per injection) was combined with 1.7 mg/kg per injection of LY122771-72, LY127123, or 2-(alpha-hydroxybenzyl)benzimidazole (HBB) and 17 mg/kg per injection of 2-guanidino-benzimidazole (GB), significant activity resulted with 2-8 treatments begun 58 h after infection. The same treatment schedule using 136 mg/kg per injection of LY122771-72, 90 mg/kg per injection of LY127123, 136 mg/kg per injection of HBB and 68 mg/kg per injection of GB produced no effect. Guanidine-associated tremors were also enhanced by the addition of the substituted benzimidazoles. When guanidine was reduced to 48 mg/kg per injection, 34 mg/kg per injection of LY122771-72 was required to produce a significant reduction in the death rate and no tremors were observed. |
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Keywords: | antipicornavirus 2-(α-hydroxybenzyl)benzimidazole LY122771-72 LY127123 2-guanidino-benzimidazole |
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